EP1116025A1 - Method, system and device for producing signals from a substance, in particular electric signals, characteristic of said substance biological and/or chemical activity - Google Patents
Method, system and device for producing signals from a substance, in particular electric signals, characteristic of said substance biological and/or chemical activityInfo
- Publication number
- EP1116025A1 EP1116025A1 EP99946227A EP99946227A EP1116025A1 EP 1116025 A1 EP1116025 A1 EP 1116025A1 EP 99946227 A EP99946227 A EP 99946227A EP 99946227 A EP99946227 A EP 99946227A EP 1116025 A1 EP1116025 A1 EP 1116025A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- biological
- substance
- signals
- transducer
- characteristic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N37/00—Details not covered by any other group of this subclass
- G01N37/005—Measurement methods not based on established scientific theories
Definitions
- Method, system and device for producing from a substance signals, in particular electrical signals, characteristic of the biological and / or chemical activity of said substance are known.
- the present invention relates to a method, a system and a device for producing from a substance signals, in particular electrical signals, characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance or an active element contained in said substance.
- the invention also relates to a method and system for monitoring said signals.
- the invention also relates to the applications of said method, system and device, in particular to the production of active substances and to the detection of determined substances.
- the invention relates to the signals linked to a biological and / or chemical activity, thus produced by said methods, system and device. We know, since the research work of Mr.
- Electromagnetic signal characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance and / or of said active element contained in said substance.
- the expression “electrical signals characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of the said substance or of an active element contained in the said substance” is also understood to mean the electrical signals derived by scanning and / or signal processing.
- characteristic in the sense that the physical parameters of the electrical signals are specific to the substance or to the active element contained in said substance and that the application of these electrical signals, via a transducer, to a system biological control allows
- Patent application WO 94/17406 published on August 4, 1994 describes a method and a device for picking up "an electromagnetic signal characteristic of a biological and / or chemical activity or of a biological and / or chemical behavior" from an active biological and / or chemical element such as a chemical compound, a cell or a microorganism, or from a substance containing this active element such as a purified preparation, a biological sample, a living being.
- an active biological and / or chemical element such as a chemical compound, a cell or a microorganism, or from a substance containing this active element such as a purified preparation, a biological sample, a living being.
- the inventors have since discovered that it is possible to improve the quality of the electromagnetic signal picked up as well as the reliability of the process for producing these signals and that it is therefore possible to produce characteristic electrical signals susceptible of industrial applications. The production of such characteristic electrical signals is of exceptional industrial importance.
- an excitation field such as for example an electromagnetic field of uniform spectral power over a frequency range (for example white noise from 1Hz to 20kHz) makes it possible to '' improve the performance of characteristic electrical signals.
- a first transducer mention may be made of very sensitive small coils of copper wire with an impedance of 300 ohms, of internal diameter 6 mm, external diameter 16 mm, length 6 mm, usually used as telephone sensors.
- the method according to the invention further comprises the step of processing said signals coming from said first transducer, as a function of second signals coming from a second transducer receiving the field specific excitation, in the absence of said substance.
- the processing may consist in subtracting these two signals using two receiver coils connected in series and in phase opposition, one facing said substance and receiving the electromagnetic field through said substance and the other receiving the electromagnetic field live.
- the processing can consist in consecutively recording the signals coming from said substance then the signals coming from a neutral substance (water or physiological saline) and then subtracting from the first second signals (which serve as a reference), this subtraction being carried out before or after processing the signals as described below (subtraction of the amplitudes or spectral powers).
- the method according to the invention comprises the step of processing the signals coming from said first transducer, as a function of the characteristics of the specific excitation field.
- signal processing consists of calculating the spectral power using a Fourier transform, truncating the useful frequency band (bandpass filter), normalizing with respect to the spectral power of the field of specific excitation, to reconstruct a signal using an inverse Fourier transform.
- the part of the signals properly characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance or of said active element contained in said substance is thus reinforced. compared to that produced without treatment.
- the specific excitation field has the characteristic of having a uniform spectral power over a frequency band.
- the spectral power is uniform over a frequency band 1Hz to 20kHz.
- said substance is subjected to a neutral excitation field of the white noise type.
- the zone subjected to the specific excitation field is isolated from the parasitic fields coming from the environment.
- the invention also relates to the applications of the signals produced.
- the method further comprises the step of applying to a receiving biological system, by means of a third transducer, said signals coming from said first transducer.
- said signals are processed, it is the signals thus processed which are applied to the receiving biological system.
- said third transducer will generate and emit an electromagnetic field towards receptor biological systems such as a carrier material or a reactive medium producing stereochemical molecules.
- the invention also relates to the control of characteristic electrical signals.
- the method further comprises the step of controlling the correlations between on the one hand, the signal coming from said first transducer or the processed signal and on the other hand, the biological and / or chemical activity or the biological behavior and / or chemical of said substance or of said active element contained in said substance.
- This control is carried out by applying, by means of said third transducer, the signals coming from said first transducer to a biological control system and by verifying that said biological control system reacts specifically to the signals coming from said first transducer.
- said signals are processed, it is the signals thus processed which are applied to said biological control system.
- the reaction of said biological control system must be related to the nature of the biological and / or chemical activity or the biological and / or chemical behavior of said substance or of said active element contained in said substance from which the signals from said first are derived. transducer.
- a biological control system an isolated guinea-pig heart, a ligand / receptor pair, in particular an antigen / antibody pair, the skin of a living guinea-pig or rabbit which is subjected to a skin injection test, isolated or cultured cells.
- the method according to the invention for producing characteristic signals delivers usable signals from an active substance, the active element of which can even be contained in low or very low concentration (less than 10 "6 moles per liter).
- the method according to the invention can therefore be applied to characterize the presence of a trace active element in a substance.
- the invention also relates to a system for producing signals, in particular signals. electrical signals, characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of a substance or of an active element contained in said substance.
- the invention also relates to a system for implementing the properties of such signals. Said system comprises a transmitter generating a specific excitation field of an electrical, magnetic and / or electromagnetic nature in an area where said substance is located.
- Said system also comprises a first transducer receiving fields resulting from the interaction of said specific excitation field and said substance, said first transducer transforming said resulting fields into signals, in particular electrical signals.
- a transducer such as a small coil of very sensitive copper wire with an impedance of 300 ohms, of internal diameter 6 mm, of external diameter 16 mm, of length 6 mm, usually used as a telephone sensor.
- the characteristics of the electrical signals leaving the transducer are as follows: amplitude of approximately 200 mV peak to peak.
- the system further includes transmission means for applying said signals from said first transducer to a receiving biological system.
- transmission means for applying said signals from said first transducer to a receiving biological system.
- Examples of receptor biological systems have been cited previously.
- the system according to the invention further comprises means for processing said signals coming from said first transducer, as a function of the signals coming from a second transducer receiving the specific excitation field, in the absence of said substance.
- said processed signals are more characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance or of said active element contained in said substance.
- the system further comprises means for processing the signals coming from said first transducer, according to the characteristics of the specific excitation field.
- said processed signals are more characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance or of said active element contained in said substance.
- said specific excitation field has the characteristic of having a uniform spectral power over a frequency band.
- the system according to the invention further comprises means for isolating said zone from the stray fields coming from the environment.
- the system according to the invention furthermore comprises control means for controlling the correlations between on the one hand, the signal coming from said first transducer or the processed signal and on the other hand, the biological and / or chemical activity or the biological and / or chemical behavior of said substance or of said active element contained in said substance.
- Said control means comprise a third transducer applying the signals coming from said first transducer to a biological control system. In the case where the signals are processed, it is the processed signals which are applied to the biological control system.
- Said control means further comprise means for verifying that the biological control system reacts specifically to the signals coming from said first transducer, according to the nature of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance or of said active element contained in said substance from which the signals from said first transducer are derived.
- biological control system an isolated guinea pig heart, a couple ligand / receptor, in particular an antigen / antibody pair, an injectable material causing skin reactions, isolated or cultured cells.
- the system according to the invention is such that said substance contains an active element in low concentration or very low concentration.
- the invention also relates to a device for producing signals, in particular electrical signals, characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of a substance or of an active element contained in said substance.
- Said device comprises a transmitter generating a specific excitation field of an electrical, magnetic and / or electromagnetic nature in an area where said substance is located. It also includes a first transducer receiving fields resulting from the interaction of said specific excitation field and said substance. Said first transducer transforms said resulting fields into signals, in particular electrical signals. Said signals are characteristic of the biological and / or chemical activity or of the biological and / or chemical behavior of said substance or of said active element contained in said substance.
- the device according to the invention further comprises means for processing said signals coming from said first transducer, as a function of the signals coming from a second transducer receiving the specific excitation field, in the absence of said substance.
- the device according to another alternative embodiment of the invention further comprises means for processing the signals coming from said first transducer, as a function of the characteristics of the specific excitation field.
- said specific excitation field has the characteristic of having a uniform spectral power over a frequency band.
- the device according to the invention further comprises means for isolating said zone from the stray fields coming from the environment.
- the invention also relates to the applications of the method, system or device described above. More particularly, the invention relates to the production of active substances, in particular the production of drugs. Said active substances are produced by applying said signals from said first transducer to a carrier substance. In the case where said signals are processed, it is the signals thus processed which are applied to the carrier substance.
- the invention also relates to the application of the method, system or device which has as its object the establishment of a table of correspondence between the characteristic signals originating from a given substance or from an active element contained in said given substance and the modifications they can induce on test biological systems.
- correspondence tables also fall within the scope of the invention, as well as the use of such correspondence tables for detecting said determined substance or said active element contained in said determined substance. This detection can in particular be carried out remotely, after transmission of said characteristic signal to a test laboratory having biological test systems.
- Correspondence tables can also be used to control the production of homeopathic products, making it possible to verify their activity during the successive dilution phases.
- the invention also relates to the electrical signals linked to a biological and / or chemical activity, obtained by implementing the method, the system or the device according to the invention. It is possible to characterize these signals by the effects they produce on a biological control system as described above. Other characteristics and advantages of the invention will appear on reading the description of variant embodiments of the invention, given by way of non-limiting example, as well as on reading the examples of experiments which have enabled to validate the process for producing characteristic electrical signals, which is the subject of the present invention, and which refers to the appended drawings in which:
- FIG. 1 represents a diagram of an exemplary embodiment of a system and a device for producing characteristic electrical signals, said system comprising an applicator making it possible to apply the characteristic electrical signals to a receiving biological system,
- FIG. 1a represents a detailed perspective view of a part of the device for producing electrical signals, showing the excitation field transmitter and the transducer receiving the resulting fields,
- FIG. 1b shows in block diagram form the type of microcomputer used either to generate the excitation fields, or to record and transmit in digitized form the characteristic electrical signals, or to apply the characteristic electrical signals to systems biological receptors via transducers,
- FIG. 1 c represents a detailed perspective view of a part of the applicator intended for applying the characteristic electrical signals to biological receptor systems
- FIG. 2 shows a diagram of an exemplary embodiment of an applicator for controlling the presence of characteristic electrical signals from an acetylcholine solution by applying them to a biological control system consisting of an isolated guinea pig heart perfused,
- FIG. 3 shows a diagram of an exemplary embodiment of a applicator for applying the characteristic electrical signals from a solution containing as active biological element Escherichia coli Kl, Streptococcus or an antibody directed against the polysaccharide antigen of Escherichia coli Kl.
- - Figure 3a shows a black and white image of 320 pixels x 240 pixels of the precipitates formed during the precipitation reaction between the polysaccharide antigen of Escherichia coli Kl and an antibody directed against this antigen, after application of the signals electrical characteristics from a biological system containing Streptococcus,
- FIG. 3b shows a black and white image of 320 pixels x 240 pixels of the precipitates formed during the precipitation reaction between the polysaccharide antigen of Escherichia coli Kl and an antibody directed against this antigen, after application of the signals electrical characteristics from a biological system containing
- FIG. 3c shows a black and white image of 320 pixels x 240 pixels of the precipitates formed during the precipitation reaction between the polysaccharide antigen of Escherichia coli Kl and of an antibody directed against this antigen, after simultaneous application of the characteristic electrical signals originating from a biological system containing Streptococcus and originating from a biological system containing an antibody directed against VEscherichia coli Kl,
- FIG. 3d shows a black and white image of 320 pixels x 240 pixels of the precipitates formed during the precipitation reaction between the polysaccharide antigen of Escherichia coli Kl and an antibody directed against this antigen, after simultaneous application of the characteristic electrical signals from a biological system containing VEscherichia coli Kl, and from a biological system containing an antibody against VEscherichia coli Kl,
- FIG. 4 shows an image of the subcutaneous allergy reaction of a guinea pig skin after injection of 0.1 ml of distilled water, the distilled water having been previously subjected to an applicator of characteristic electrical signals from a neuromediator such as acetylcholine (ACh).
- a neuromediator such as acetylcholine (ACh).
- FIGS. 1, la, lb and le there is shown diagrammatically an alternative embodiment of a system making it possible to produce characteristic electrical signals and to use them for industrial purposes.
- These signals are characteristic, within the meaning of the present invention, of the biological and / or chemical activity or of the biological and / or chemical behavior of a substance.
- the system comprises a device 10 for producing electrical signals characteristic of the biological and / or chemical activity or of the biological and or chemical behavior of a substance 1 or of an active element contained in said substance.
- la, lb and said substance 1 is a solution of caffeine 10 "6 M.
- the device 10 located in Paris for example, produces characteristic electrical signals which are digitized after analog-digital conversion.
- the signals thus digitized are, in a manner known per se, transmitted remotely, for example by a computer communication network of the internet type implementing radio links 11.
- the digitized signals thus transmitted are received by an applicator 12, located in New York for example, comprising transmission means 13.
- the transmission means 13 make it possible to apply the characteristic signals (after digital-analog conversion) to a receptor biological system.
- the receptor biological system is a diet drink.
- the digitized signals can be processed 27, recorded and stored 33 prior to their remote transmission and / or before being applied to a receiving biological system.
- the signal production device 10 comprises an enclosure 2 provided with an electrical and magnetic shielding isolating it from the stray fields coming from the environment.
- the shielded cylindrical enclosure is made up of three superimposed layers: copper, soft iron, mumetal, made of sheet metal 1mm thick.
- the enclosure has an internal diameter of
- a transmitter 4 is located inside the enclosure. It generates a specific excitation field of an electromagnetic nature.
- the transmitter is powered by a generator 14.
- a glass tank 3 having the dimension 10mm x 10mm x 45mm. This tank 3 contains
- the emitter 4 comprises a coil advantageously supplemented by a soft iron magnetic core.
- the emitting coil 4 has an impedance of 300 ohms, an inside diameter of 6 mm, an outside diameter of 16 mm, a length of 6 mm.
- the soft iron magnetic core is placed in contact with the outer walls of the tank 3. Said substance is thus subjected to the excitation field emitted by the transmitter 4.
- the generator 14 is designed to generate a low frequency signal in particular square signals or low frequency sine waves, pink noise or, advantageously, white noise.
- the spectrum of the excitation signal supplying the emitting coil 4 corresponds substantially to the spectrum of audible frequencies (20 Hz - 20,000 Hz).
- the generator 14 can be an analog signal generator of known type, using for example a read only memory (ROM, PROM, EPROM, EEPROM in English terminology) containing the digital signal of the desired noise. This memory is connected in a manner known per se to a digital-analog converter.
- ROM read only memory
- PROM PROM
- EPROM EPROM
- EEPROM electrically erasable programmable read-only memory
- One can for example use a computer 14 of the PC type, operating under the WINDOWS ® operating system 95 of the Company MICROSOFT and comprising, in addition to the sound card 25 a microprocessor 27, an input / output interface 29, a controller 31 of a mass memory 33 and a video interface 35 connected by one or more buses 37.
- the digital analog converter 41 of the sound card 25 has an output terminal 8.
- the output terminal 8 of the microcomputer sound card 14 is connected to the input terminal 8 'of the transmitter 4, via an amplifier 15 whose characteristics are the following: bandwidth from 10 Hz to 20 kHz, gain 1 to 10, input sensitivity +/- 1 V.
- an amplifier 15 whose characteristics are the following: bandwidth from 10 Hz to 20 kHz, gain 1 to 10, input sensitivity +/- 1 V.
- the Soundblaster 16 card sold by CREATIVE LABS.
- the transducer 6 located inside the enclosure 2, receives the fields resulting from the interaction of said specific excitation field and said substance 1.
- the transducer 6 transforms said resulting fields into electrical signals. These electrical signals are present, at the output terminals 9 ′ of the transducer 6, in the form of a variable potential difference or an electric current of variable intensity.
- the transducer 6 comprises a coil having a soft iron core. This coil 6 has an impedance of 300 ohms, an inside diameter of 6 mm, an outside diameter of 16 mm, a length of 6 mm.
- the soft iron magnetic core is placed in contact with the outer walls of the tank 3.
- the characteristic electrical signals available at the output of the transducer 6 are amplified by a preamplifier 16.
- the amplifier-preamplifier 16 has the following characteristics: bandwidth from 10 Hz to 20 kHz, gain 50 to 100 for sensitivity input +/- 100 mV or gain 500 to 2000 for an input sensitivity of +/- 5 mV (to be used in the case of a "opposition series" connection of a second transducer).
- the characteristic electrical signals can be recorded 31, stored 33, transferred 11, 29 remotely by implementing the known technologies of electronics, data processing and telecommunications.
- the recording of the characteristic electrical signals, or that of the electrical signals which derive therefrom after amplification or processing, can be carried out in analog by a signal recorder, in particular on magnetic tape, adapted to the frequencies of the characteristic electrical signals at the output of the transducer 6 As the bandwidth used corresponds to the audio band, it is possible in particular to use a tape recorder.
- the output terminal 9 ′ of the signal production device 10 is connected to the microphone input or to the line input of such a tape recorder.
- the characteristic electrical signals recorded are collected at an output terminal, in particular at the line output or at the speaker output of the tape recorder.
- a digital recording of the characteristic electrical signals is carried out after analog-digital conversion of said signals.
- a microcomputer 17 is used, provided with a signal acquisition board 25.
- a PC type computer 17 operating under the WINDOWS ® operating system 95 of the MICROSOFT Corporation
- This microcomputer can be of the same type as that used to generate the excitation field. It can be the same microcomputer. In this case it comprises, in addition to the sound card, an acquisition card 25, a microprocessor
- the acquisition card 25 comprises an analog-digital converter 39 having, from preferably a resolution higher than 12 bits, advantageously equal to 16 bits, as well as a sampling frequency twice the maximum frequency that we want to be able to digitize, for example 44kHz.
- the output 9 'of the transducer 6 is connected to the input 9 of the analog-digital converter 39 via the preamp 16. All the connections are made in shielded cable. All devices are grounded.
- the Matlab software from the company "The Math Works” is used to process the characteristic electrical signals or the signals derived therefrom.
- the output of the device 10 for producing characteristic electrical signals is connected to the input 9 of the analog-digital converter 39 of the card 25 of the computer 17.
- the characteristic electrical signals are acquired for a period of time, for example between 1 and 60 s (for example 6 sec) and the digital file is recorded in a mass memory 33, for example in the form of a sound file in WAV format.
- This file may possibly undergo digital processing, such as for example digital amplification for signal level calibration, filtering for the elimination of unwanted frequencies, or be transformed into its spectrum by a discrete FOURIER transform, preferably by l 'fast FOURIER transform algorithm (FFT "Fast Fourier Transform" in English terminology).
- digital processing such as for example digital amplification for signal level calibration, filtering for the elimination of unwanted frequencies, or be transformed into its spectrum by a discrete FOURIER transform, preferably by l 'fast FOURIER transform algorithm (FFT "Fast Fourier Transform" in English terminology).
- the duration of the signal produced can be increased by repeating in a file several times a fragment or the entire sound file originally produced.
- These means for processing the characteristic electrical signals can be used to improve the performance of said characteristic electrical signals.
- a second transducer of the same type as that described above is provided. This second transducer transforms the excitation field into electrical signals, in the absence of the said substance. These electrical signals are subtracted by a series connection opposite to the signals coming from the first transducer. This gives more representative signals of the interaction of the specific excitation field and the substance.
- the processing means take into account the characteristics of the specific excitation field and retreat the characteristic electrical signals in the following manner.
- preamplifier 16 already constitute in themselves products capable of industrial applications. They can be amplified, processed, recorded, stored, transferred remotely by implementing known technologies in electronics, data processing and telecommunications. We have seen for which industrial applications they could be used in particular.
- the file of the characteristic electrical signals, recorded in digital form as just described, possibly after processing, can be transferred remotely by a computer communication network.
- This network may include microwave links 11.
- the file characteristics and electrical signals transmitted is saved by the mass memory of the microcomputer 18. It is for example a PC type computer operating under the WINDOWS ® operating system 95 of the MICROSOFT Company.
- This microcomputer 18 can be of the same type as that used to generate the excitation field.
- the characteristic signal file thus transmitted and recorded can be used, in a manner known per se, to produce analog characteristic electrical signals.
- the file possibly processed is transformed by a digital-analog converter 41 of the card 25 (or of a separate card) of the computer 18.
- the digital-analog converter 41 delivers on its output 8 analog electrical signals characteristic of the biological activity of the substance from which they are derived. These signals can be transformed, as will be described below, into electromagnetic fields and applied to biological systems.
- Bottle 50 contains the receptor biological system. This consists, for example, of 10ml of distilled water for injection (Biosedra or other brands) in a 15ml polypropylene polypropylene tube (Falcon, Becton Dickinson 2097). This bottle is placed in an electromagnetic field radiated by a transducer 51, typically a coil.
- a transducer 51 typically a coil.
- the coil has, for example, a length of 120 mm, an inside diameter of 25 mm, an outside diameter of 28 mm, has 631 turns of a wire with a diameter of 0.5 mm and a resistance of 4 ohms.
- the coil 51 is connected to ground. Without this representing any limiting character, the coil 51 of the transducer has a vertical axis allowing the introduction of the bottle 50 containing the receiving biological system.
- the input terminals 8 ′ of this coil 51 are connected, in the case of the variant embodiment described, to the output 8 of the analog-digital converter 41 of the microcomputer 18 via an amplifier 19 having the following characteristics: bandwidth from 10 Hz to 20 kHz, gain 1 to 20, input sensitivity 250mV, output power RMS 60W at 8 ohms, signal to noise ratio 80dB.
- the voltage across the coil 51 has an amplitude of 5 effective volts and the signal is applied for 10 min.
- the input terminals 8 ′ of the applicator can also be, in the case of certain variant embodiments, directly connected to the output of the preamplifier 16 or to the output 8 of the digital-analog converter 41 of the computer 17.
- the invention also relates to the methods making it possible to control the correlations between on the one hand, said signal the signal coming from the transducer 6 and on the other hand, the biological and / or chemical activity or the biological and / or chemical behavior of said substance or of said active element contained in said substance.
- This control is carried out by applying, by means of a transducer of the type described with reference to FIG. 1 a, the signals coming from the transducer 6 to a biological control system and by verifying that said biological control system reacts specifically to signals from said first transducer.
- said signals are processed, it is the signals thus processed which are applied to said biological control system.
- the reaction of said biological control system must be related to the nature of the biological and / or chemical activity or the biological and / or chemical behavior of said substance or of said active element contained in said substance from which the signals from said first are derived. transducer.
- calcium ionophore A 23187 (Sigma C-7522) (I) at a concentration of 10 "6 M in distilled water for injection (for example of the Biosedra brand).
- the substances were placed in the tank 3 of the enclosure 2 and their characteristic electrical signals were acquired in accordance with the operating process described with reference to Figures 1, la and lb .
- the three characteristic electrical signals produced as described above were applied to the guinea-pig heart, by connecting the terminals 8 'of the coil 60 to the output of the amplifier 19 of power 60W.
- the three characteristic signals were applied for 2 min at a voltage of 5 Veff.
- the fraction collector collected the tubes allowing the flow rate of the guinea pig heart to be measured at the rate of one tube per minute.
- the buffer solution passing through the heart had the following composition: 2 mM CaCl, 25 mM NaHC03, 118 mM NaCl, 4.7 mM Kcl, 1.2 mM MgSO4, 1.2 mM KHP04, 11 mM Glucose, 2 mM Pyruvate.
- the table below indicates (in ml) the quantity of buffer solution recovered in the collecting tubes over time.
- the acquisition of the electrical signal characteristic of the biological activity of Streptococcus was carried out by placing in the center of the enclosure 2 a tank 3 containing 1 ml of an aqueous suspension of previously formulated Streptococcus bacteria (6.10 6 cf u / ml) .
- MENINGITIS Reference 61709 - SANOFI DIAGNOSTICS PASTEUR. The tests were carried out using as reagents:
- transducer 151 consisting of a coil measuring 120 mm long and 25 mm internal diameter, having 631 turns and a resistance of 4.7 Ohm and connected by its 8 ′ input to the output 8 of the digital-analog converter 41 of a Soundblaster card of a computer 17 (one could also use a computer 18 located remotely) restoring the recording files made up of the electrical signals which one wishes to apply the necessary time to bring this transducer to the temperature of 37 ° C; - a drop 145 (i.e.
- 40 to 50 ⁇ l is deposited on a blade 147 provided with a capillary 149 in the form of a serpentine (of the type provided in the PASTOREX MENINGITIS kits), a short distance from the opening of the latter ) of the antigen solution as described in point b) above, as well as a drop 143 (also corresponding to a volume of 40 to 50 ⁇ l) of latex sensitized by the antibody, taking care that these drops do not mix.
- a serpentine of the type provided in the PASTOREX MENINGITIS kits
- the desired electrical signal (s) are applied to the two drops of reagents thus deposited by placing the slide in the center of the transducer 151 for approximately 2 minutes and by restoring a sound file using the computer 17 (or the 'computer 18 located remotely),
- the two drops of reagents 143, 145 are mixed for approximately 10 seconds and the reaction mixture is allowed to migrate into the capillary for approximately 13 minutes and the precipitation reaction takes place;
- This reading is performed by analysis using a software analysis and image processing implemented on a PC computer running the WINDOWS ® 95 operating system (Microsoft), an image acquired at using a video camera positioned on an optical microscope and connected to said computer by a video capture card.
- the camera works in grayscale.
- a first treatment increases the contrast, the threshold being adjusted so that the precipitates appear in black, while the areas devoid of latex particles or precipitates appear in white.
- the computer determines a precipitation index (I) calculated according to the formula: Surface area of precipitates larger than 60 pixels
- the test for monitoring the presence of a signal characteristic of the biological activity of Escherichia coli is considered positive when, during an experiment, the application of the electromagnetic signals characteristic of the biological activity of Escherichia coli and / or of the biological activity of its specific antibody leads to the obtaining of a precipitation index significantly (at least 40%) greater than the maximum of those obtained, under the same conditions, and for example on 3 experiments, after application of the electrical signal characteristic of the biological activity of Streptococcus.
- Table A below presents the precipitation indexes obtained in a first series of tests aimed at comparing the effects of the application of electrical signals characteristic of the biological activity of Escherichia coli (E. coli) originating from a system biological containing VEscherichia coli to those observed after application, under the same reaction conditions, of electrical signals characteristic of the biological activity of Streptococcus (St) coming from a biological system containing Streptococcus, and this, for 3 different dilutions (1 / 7, 1 / 7.5 and 1/8) of the solution of the Escherichia coli K1 polysaccharide antigen used as reagent in the precipitation reactions.
- E. coli Escherichia coli
- St Streptococcus
- FIGS. 3a and 3b show, by way of example, images of the precipitates formed on the one hand, after application of the electrical signal characteristic of the biological activity of Streptococcus (FIG. 3a) and, on the other hand, after application of the electrical signal characteristic of the biological activity of Escherichia coli ( Figure 3b). These images correspond respectively to the precipitation indexes of 32 and 117 which are reported in the 5th row of Table A.
- Table B below presents the precipitation indices obtained in a second series of experiments in which the effects of the simultaneous application of the electrical signal characteristic of the biological activity of Escherichia coli and of the electrical signal characteristic of the biological activity of the antibody directed against Escherichia coli on the other hand, were compared with those of the simultaneous application, under the same reaction conditions, of the electrical signal characteristic of the biological activity of Streptococcus and the electrical signal characteristic of the biological activity of the antibody directed against Escherichia coli on the other hand and this, for 2 different dilutions (1/7 and 1 / 7.5) of the solution of Escherichia polysaccharide antigen coli Kl used as reagent.
- Figures 3c and 3d also show, by way of example, images of the precipitates which correspond respectively to the precipitation indexes of 71 and 247 reported in the second row of Table B. All these results clearly demonstrate the ability that presents a ligand / receptor pair to reveal and control the presence of an electrical signal characteristic of the biological activity of a ligand and / or its receptor. Indeed, in the presence of a specific characteristic signal of the ligand / ligator couple or of one of the elements of this couple, the formation of the complexes formed by the reaction between this ligand and this receptor is amplified. This amplification is very specific, since the electrical signal characteristic of the biological activity of a biologically active element, but foreign to this reaction, does not itself produce an amplification effect.
- the term “ligand / receptor couple” means any couple formed by two substances capable of recognizing each other specifically, of binding and reacting together by forming complexes.
- it may be an antigen / antibody or hapten / antibody pair in which the ligand (the antigen or the hapten) may be a biological compound (protein, enzyme, hormone, toxin, tumor marker), a chemical compound (toxic or medicinal active ingredient for example), or a cellular or particulate antigen (cell, bacteria, virus, fungus, etc.), the receptor possibly being a soluble antibody or a membrane receptor.
- the receptor possibly being a soluble antibody or a membrane receptor.
- It can also be a couple formed by an enzyme and its specific substrate.
- correspondence tables can be subsequently used to detect active elements by analyzing the effects of the characteristic signals originating from them on the test biological systems appearing in the correspondence table.
- a living guinea pig is used, to which is injected intravenously with a blue dye (Evans blue - Sigma E 2129) which binds to blood albumin.
- Albumin does not leave the vessels, unless there is inflammation, therefore vasodilation and permeation of the vessels, the typical example of such a reaction in humans being urticaria.
- the test is carried out by injecting 0.1 ml of the solution, the activity of which must be monitored, under the skin of the animal thus prepared. The diameter of the blue spots that appeared around the injection points is then measured. To do this, we scan the skin, then save the bitmap image file. Then the size of the blue spots due to the reaction is evaluated.
- the presence of signals characteristic of the biological activity of the neuromediator acetylcholine (ACh; Sigma A2661) in solution in a physiological solution was checked, analyzing the effects on guinea pig skin
- the acquisition of the electrical signal characteristic of the biological activity of acetylcholine was carried out by placing in the center of enclosure 2 a tank 3 containing 1 ml of a solution of acetylcholine in distilled water at the concentration delO "6 M.
- the acquisition of the electrical signals characteristic of the biological activity of the acetate / acetylcholine mixture was carried out by operating in the same way, but using a tank 3 containing 1 ml of a solution of acetate / acetylcholine in water. distilled at a concentration of 10 "6 M.
- the coil 51 of FIG. 1 is used as the applicator.
- the numbers which appear in the first column of Tables C, D, and E below correspond to the references of figure 4.
- Experiments numbers 200 to 204 show that the distilled water solutions injected after application of the ACh signal trigger a significant skin reaction (average of 11 mm) compared to the same distilled water solutions injected without application of the ACh signal. The latter do not trigger a reaction as shown in experiments numbers 300 to 306 (3mm).
- Experiments numbers 400 to 404 and 410 to 412 in Table E are carried out using a product close to acetylcholine but inactive: the acetate / choline mixture (A-C).
- Experiments 410, 411, 412 correspond to an injection of a 10 "6 M weight AC solution. It is found that an injection of distilled water solution after application of the AC signal (exp. 400 to 404) and that a weight injection (exp. 410, 411, 412) does not trigger any effect (diameter between 1 and 3 mm). These injections show that the skin reaction of the guinea pig is very specific to the nature of the substance in solution because these injections, performed under the same conditions as injections numbers 200 to 202, have no effect.
- the homeopathic product to be tested is a solution
- a 1 ml sample is recorded as described in this patent.
- a solution is prepared beforehand, for example 5 ml, by diluting 2 granules per ml of distilled water for injectable preparation (for example of the Biosedra brand), and one then proceeds to the registration of an IMI sample by the method described in this patent.
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Abstract
Description
Claims
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9812058A FR2783605A1 (en) | 1998-09-23 | 1998-09-23 | Production of electromagnetic signals from a biological or chemical sample, characteristic of their active ingredients, which can then be transmitted to a remote location |
| FR9812058 | 1998-09-23 | ||
| PCT/FR1999/002270 WO2000017638A1 (en) | 1998-09-23 | 1999-09-23 | Method, system and device for producing signals from a substance, in particular electric signals, characteristic of said substance biological and/or chemical activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1116025A1 true EP1116025A1 (en) | 2001-07-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP99946227A Ceased EP1116025A1 (en) | 1998-09-23 | 1999-09-23 | Method, system and device for producing signals from a substance, in particular electric signals, characteristic of said substance biological and/or chemical activity |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US6541978B1 (en) |
| EP (1) | EP1116025A1 (en) |
| AU (1) | AU5867399A (en) |
| FR (1) | FR2783605A1 (en) |
| WO (1) | WO2000017638A1 (en) |
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| WO2013026837A1 (en) | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
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| FR2811591B1 (en) * | 2000-07-12 | 2014-11-07 | Digibio | METHOD AND DEVICE FOR PREVENTING THE ALTERATION OF A SUBSTANCE HAVING BIOLOGICAL ACTIVITIES |
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| FR2893418A1 (en) * | 2006-06-02 | 2007-05-18 | Bruno Robert | Use of electromagnetic signal emitted by diluted and filtered biological medium modified by exposing medium to amplified signal |
| FR2894673B1 (en) * | 2005-12-14 | 2014-10-31 | Luc Montagnier | METHOD FOR CHARACTERIZING A BIOCHEMICAL ELEMENT HAVING BIOLOGICAL ACTIVITY BY ANALYZING LOW FREQUENCY ELECTROMAGNETIC SIGNALS |
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| US8405379B1 (en) | 2008-09-18 | 2013-03-26 | Luc Montagnier | System and method for the analysis of DNA sequences in biological fluids |
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- 1998-09-23 FR FR9812058A patent/FR2783605A1/en not_active Withdrawn
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1999
- 1999-09-23 US US09/787,570 patent/US6541978B1/en not_active Expired - Lifetime
- 1999-09-23 WO PCT/FR1999/002270 patent/WO2000017638A1/en not_active Ceased
- 1999-09-23 EP EP99946227A patent/EP1116025A1/en not_active Ceased
- 1999-09-23 AU AU58673/99A patent/AU5867399A/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0017638A1 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012146628A1 (en) | 2011-04-29 | 2012-11-01 | Roche Glycart Ag | Novel immunoconjugates |
| WO2013026837A1 (en) | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific t cell activating antigen binding molecules |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2783605A1 (en) | 2000-03-24 |
| WO2000017638A1 (en) | 2000-03-30 |
| AU5867399A (en) | 2000-04-10 |
| US6541978B1 (en) | 2003-04-01 |
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